TO THE EDITOR
Surgical resection of intestinal tumors substantially improves patient survival[1]. However, the profound physiological stress and psychological burden during the perioperative period create an “emotional vulnerability window” in which anxiety and depression are highly prevalent, particularly in the early postoperative phase[2,3]. A 2024 systematic review and meta-analysis of patients with colorectal cancer (CRC) reports that anxiety and depression are associated with an increased risk of mortality, indicating that postoperative psychological disorders are neither benign nor self-limiting and that their clinical significance has long been underestimated[4]. Concurrent clinical studies further show that higher levels of pre- and postoperative anxiety and depression are associated with delayed recovery, a greater complication burden, and poorer health-related quality of life (QoL), underscoring the need for continuous assessment and early psychological intervention[5].
We read with great interest the prospective cohort study by Wei et al[6] published in World Journal of Gastroenterology. This study integrated a three-tier chain of evidence - mixed-effects models, mediation analysis, and an extreme gradient boosting algorithm - supplemented by health-related QoL network analysis, to dynamically characterize trajectories of depression and anxiety in patients after intestinal tumor surgery during longitudinal follow-up. Its primary objective is to elucidate the relationships between psychological status and inflammatory activation, nutritional status, and health-related QoL. While these methodological innovations are noteworthy, we seek to situate the study’s contributions within a broader academic context, highlight key limitations, and propose potential pathways for clinical translation that may facilitate practical implementation.
RESEARCH OVERVIEW AND REINTERPRETATION FROM THE GUT-IMMUNE-BRAIN AXIS PERSPECTIVE
The prospective observational study by Wei et al[6] included 120 patients undergoing intestinal tumor surgery. Emotional symptoms (Hamilton Depression Scale, Self-Rating Anxiety Scale), inflammatory and nutritional markers [neutrophil-to-lymphocyte ratio (NLR), albumin-to-fibrinogen ratio (AFR), platelet-to-neutrophil ratio, hematocrit-to-albumin ratio] and health-related QoL (36-Item Short Form) were assessed on the 3rd, 7th, 30th, and 90th days after surgery. Over time, emotional symptoms and NLR decreased significantly, while AFR and 36-Item Short Form scores increased, indicating multidimensional improvements in health status and QoL.
Previous research has shown that perioperative psychological states influence clinical outcomes[7] and that AFR serves as a prognostic indicator for recurrence, survival, and perioperative risk in CRC[8]. However, most studies have concentrated on broad endpoints - such as postoperative complications and overall QoL - offering limited understanding of how AFR specifically fits within the “psychological status - QoL” pathway. By applying mixed-effects modelling and mediation analysis, Wei et al[6] introduced a novel mechanism: “psychological status - inflammation/nutrition imbalance - QoL”. Their findings show that NLR and AFR have significant indirect effects on the relationship between psychological status and QoL, thereby positioning these inflammatory and nutritional biomarkers as key mediators linking psychological vulnerability to clinical outcomes.
Furthermore, the authors developed an extreme gradient boosting-based prediction model using key surgical and perioperative variables. Multicenter external validation (n = 240) confirmed NLR, AFR, and intraoperative hypotension (IOH) as independent risk factors. Based on these findings, the study recommends monitoring NLR and AFR within 24 hours after surgery and proposes NLR > 7.0 and AFR < 12.0 as thresholds for initiating clinical intervention. Taken together, this work helps bridge a critical evidence gap from disease pathogenesis to actionable clinical targets. This biomarker-informed pathway to clinical intervention offers a novel biological framework for understanding the high prevalence of anxiety and depression among patients with CRC[9].
Previous studies indicate that patients with gastrointestinal malignancies bear a substantial psychological burden, with approximately 28%-57% developing clinically relevant anxiety or depressive symptoms during the diagnostic and treatment course[10,11]. At the mechanistic level, the gut-brain axis refers to the bidirectional communication pathway between the gastrointestinal tract and the central nervous system[12,13]. As evidence has expanded, the immune system has become recognized as a key mediator of this gut-brain crosstalk[14], leading to the development of the gut-immune-brain axis (GIBA) framework. This model proposes that changes in gut microbiota and intestinal mucosal immunity can influence the activity of immune cells in the central nervous system through mechanisms such as peripheral immune activation and neuroinflammatory signaling, ultimately influencing mood, behavior, and cognition[15]. NLR is a key indicator of systemic inflammation and immune status, whereas AFR integrates multidimensional information related to inflammation, coagulation, and nutritional reserve. Together, they function as composite peripheral blood markers of inflammatory and stress responses. An increased NLR combined with a reduced AFR indicates an adverse systemic profile characterized by a high inflammatory burden, immune dysregulation, and suboptimal nutritional status. On this basis, we may further explore how NLR, AFR, and intraoperative blood pressure fluctuations influence postoperative psychological outcomes through the GIBA framework described earlier. Patients with CRC also exhibit pronounced alterations in gut microbiota composition compared with healthy individuals[16]. Along with disease-related changes in dietary patterns, nutritional depletion, and a chronic proinflammatory state, these alterations may increase susceptibility to inflammation-related depressive symptoms even before surgery[17]. During CRC resection, surgical trauma directly activates the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, stimulating the release of cortisol, catecholamines, interleukin-6 (IL-6), and other mediators[2,18] that drive stress responses and systemic inflammation. At the same time, intestinal wall resection and anastomosis disrupt the mucosal barrier and permit the translocation of luminal antigens, further intensifying the systemic inflammatory process. IOH can simultaneously induce intestinal and cerebral hypoperfusion. The resulting intestinal ischemia-reperfusion injury compromises the gut barrier, allowing microbial products to enter the systemic circulation. In parallel, cerebral hypoperfusion, together with gut-derived microbial metabolites, alters blood-brain barrier permeability[15], making the central nervous system more vulnerable to peripheral inflammatory signals. In addition, perioperative exposure to antibiotics, opioid analgesics, and anesthetic agents further induces dysbiosis and reshapes microbial-derived metabolite profiles[19,20]. Collectively, these factors intensify peripheral inflammation and, together with aberrant microbial metabolites, disrupt central immune homeostasis. In doing so, they shape a GIBA-based regulatory model consistent with the “peripheral inflammation-central mood circuitry” framework[21]. Recent studies have also reported increased levels of tumor necrosis factor (TNF), macrophage colony-stimulating factor, and IL-12 in the intestinal mucosa of patients with depression, along with a decreased abundance of butyrate- and propionate-producing bacteria (e.g., Clostridium, Roseburia, Haemophilus)[22]. These findings support a close association between gut microbial dysbiosis and depressive states. Therefore, the dynamic changes in NLR and AFR observed in the study by Wei et al[6] may not only reflect systemic inflammation and nutritional status but also serve as peripheral indicators of GIBA activation. Although this mechanistic interpretation requires further confirmation in experimental and clinical studies, the processes outlined above, supported by existing evidence, offer a plausible pathophysiological framework for understanding the relationships among NLR, AFR, IOH and postoperative psychological states.
From the perspective of the GIBA framework, the study by Wei et al[6] provides preliminary clinical evidence linking NLR, AFR, and IOH with postoperative psychological outcomes. Methodologically, it also integrates subjective psychological scale assessments with objective biomarker measurements and multidimensional evaluations of QoL. The core value of this work lies in its innovative findings and its potential for clinical translation. To more accurately assess its contribution and support its integration into clinical practice, we next examine the strengths and limitations of its study design and outline specific directions for future refinement.
STRENGTHS AND LIMITATIONS
The study by Wei et al[6] is distinguished by a rigorous methodological design. Its prospective cohort structure and multi-timepoint, multidimensional monitoring move beyond simple cross-sectional descriptions of postoperative emotional states and help reduce the risk of model overfitting. In addition, the study innovatively integrates physiological, inflammatory, and psychological domains into a unified framework for postoperative risk prediction, thereby operationalizing a novel model of mind-body interaction. By incorporating AFR, NLR, and intraoperative hemodynamic variables into mental health risk stratification, it directly links monitorable and modifiable anesthetic and perioperative management parameters with psychological outcomes, highlighting both its methodological originality and its strong potential for clinical translation.
However, several limitations constrain its clinical translation. The relatively homogeneous and small sample size (n = 120) may introduce selection bias. Although the independent risk factors (NLR, AFR, and IOH) were validated in an external cohort from the same region (n = 240), broader validation across diverse geographic settings, surgical procedures, and complication profiles is needed to reduce center-specific effects and improve generalizability. The study also did not directly measure key inflammatory cytokines such as IL-6 and TNF-α, resulting in incomplete biomarker characterization. Future cohorts should incorporate parallel cytokine assessment to strengthen the biological foundation of the “psychological-inflammation-QoL” mediation pathway. Additionally, the 90-day follow-up period is likely insufficient for patients undergoing tumor resection, particularly those with stomas. To comprehensively assess long-term QoL, treatment adherence, and psychological adaptation, extending follow-up to at least 12 months is recommended. Future research should also examine the dynamic trajectories of chronic anxiety and fear of cancer recurrence[23], while tracking the long-term evolution of biomarkers such as NLR and AFR to confirm their value as early warning indicators of adverse clinical outcomes.
Having recognized these strengths and limitations, a central question emerges: How can risk prediction models be effectively translated into practical clinical nursing pathways and personalized intervention strategies? Achieving this transition requires both a well-defined roadmap for clinical translation and the timely formulation of future research directions.
CLINICAL IMPLICATIONS AND FUTURE RESEARCH DIRECTIONS
The study indicates that postoperative NLR > 7.0, AFR < 12.0, and intraoperative systolic blood pressure < 90 mmHg may represent critical thresholds associated with worsening postoperative emotional disturbances. These findings suggest that a graded early-warning system could be developed based on intraoperative blood pressure fluctuation patterns and dynamic perioperative biomarker changes. Such a system would allow tailored interventions for patients across different risk levels and support the creation of a comprehensive preventive strategy that addresses both physical and psychological domains.
Implement staged perioperative psychological management that includes preoperative prehabilitation[24], postoperative screening for emotional disturbances, and timely psychological support for high-risk patients. This support may involve targeted health education, brief psychological interventions, and, when necessary, psychiatric consultation and pharmacologic optimization to enhance interdisciplinary collaboration.
Optimize intraoperative blood pressure and organ perfusion management. Intraoperatively, systolic blood pressure should be maintained at ≥ 90 mmHg, and states of tissue hypoperfusion should be avoided. Through individualized blood pressure targets, judicious fluid management, and precise pharmacologic adjustment, hemodynamic stability should be preserved to prevent ischemia of vital organs.
Simultaneously manage inflammatory and nutritional status. Key measures include strengthening early postoperative nutritional support, optimizing pain control and sleep management, and implementing interventions targeting inflammation and gut microbiota dysbiosis[25,26] to improve postoperative emotional outcomes.
Establish a continuous post-discharge follow-up and support system. Patients’ emotional recovery and physical parameters should be monitored regularly via telephone or online platforms to ensure timely access to professional assistance when needed. Taken together, this systematic intervention pathway has the potential to translate risk prediction into concrete clinical nursing practices that prioritize both the physical and psychological well-being of patients.
Subsequent research could proceed in a stepwise manner, following the sequence of validation, mechanistic exploration, and intervention development. First, the reliability and generalizability of the proposed risk thresholds should be validated in a larger and more diverse patient population. Second, in-depth investigations are needed to elucidate the underlying biological mechanisms. To this end, prospective cohort studies should concurrently collect inflammatory cytokines (e.g., IL-6, TNF-α), gut microbiota profiles and their metabolites, together with standardized measures of psychological status and QoL. These efforts will further clarify the pivotal roles of NLR and AFR within the interconnected pathway linking “psychological state - inflammation/nutritional imbalance - QoL”. Finally, future research should implement randomized controlled trials guided by NLR- and AFR-based thresholds, comparing dual-pathway interventions - combining psychological support with nutritional and/or anti-inflammatory therapy - against standard perioperative care. In parallel, studies could assess the effects of alternative blood pressure management strategies on postoperative NLR and AFR levels, as well as on emotional outcomes. Additional investigations should explore the bidirectional relationships between infection and emotional status, and between tissue perfusion and emotional status, while prospectively monitoring clinical endpoints such as postoperative complication rates and hospital readmissions. Following this research trajectory, current predictive findings may ultimately be translated into an evidence-based, clinically feasible, integrated mind-body management model.
CONCLUSION
Using clinically accessible indicators, Wei et al[6] constructed a postoperative emotional-management framework characterized by “monitorability, intervenability, and predictability”. This framework shifts emotional disturbances from secondary observational endpoints to a central perioperative treatment target, thereby advancing the field from simple correlational analysis to mechanistic understanding and from generic risk prediction to precision intervention. We anticipate that subsequent multicenter, long-term follow-up studies on mechanisms and interventions by these authors will further substantiate the underlying biological pathways and clarify health-economic cost-effectiveness. Such work may refine precision prediction and intervention strategies for psychological risk after intestinal tumor surgery and help shift surgical care from “organ repair” to “mind-body integration”.
ACKNOWLEDGEMENTS
The authors are grateful to the investigators of the original study for their valuable contribution, which served as the basis for this commentary.
Peer review: Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country of origin: China
Peer-review report’s classification
Scientific quality: Grade B, Grade C
Novelty: Grade C, Grade C
Creativity or innovation: Grade C, Grade D
Scientific significance: Grade C, Grade D
P-Reviewer: Li B, PhD, Assistant Professor, China S-Editor: Hu XY L-Editor: A P-Editor: Xu ZH
